This invention relates to derivatives of propenoic acid useful as fungicides, to processes for preparing them, to fungicidal compositions containing them, and to methods of using them to combat fungi, especially fungal infections in plants.
The invention provides a compound having the formula (I): 
and stereoisomers thereof, wherein R1 is optionally substituted aryl or optionally substituted heteroaryl; Y is oxygen, sulphur or NR4; R2, R3 and R4, which may be the same or different, are hydrogen, C1-4 alkyl or C2-4 alkenyl; X is halogen (fluorine, chlorine, bromine or iodine), C1-4 alkyl, C2-4 alkenyl, C1-4 alkoxy, nitro or cyano; and n is 0 or an integer of 1 to 4; provided that when Y is oxygen, n is 0 and R1 is unsubstituted phenyl at least one of R2 and R3 is other than hydrogen or methyl.
In one aspect the invention provides compounds of the formula (I) as defined above in which Y is oxygen.
In another aspect the invention provides compounds of the formula (I) as defined above in which R1 is optionally substituted hereroaryl.
In still another aspect the invention provides compounds of the formula (I) as defined above in which R1 is optionally substituted aryl and Y is NR4.
In yet another aspect the invention provides compounds of the formula (I) as defined above in which R1 is optionally substituted aryl, Y is oxygen or sulphur but R2 and R3 are not both hydrogen.
In yet another aspect the invention provides compounds of the formula (I) as defined above in which X is C2-4 alkenyl.
The compounds of the invention contain at least one carbon-carbon double bond, and are sometimes obtained in the form of mixtures of geometric isomers. However, these mixtures can be separated into individual isomers, and this invention embraces such isomers, and mixtures thereof in all proportions including those which consist substantially of the (Z)-isomer and those which consist substantially of the (E)-isomer.
The individual isomers which result from the unsymmetrically substituted double bond of the propenoate group are identified by the commonly used terms xe2x80x9c(E)xe2x80x9d and xe2x80x9c(Z)xe2x80x9d. These terms are defined according to the Cahn-Ingold-Prelog system which is fully described in the literature (see, for example, J March, xe2x80x9cAdvanced Organic Chemistryxe2x80x9d, 3rd edition, Wiley-Interscience, page 109 et seq).
Usually one isomer is more active fungicidally than the other, the more active isomer usually being the one wherein the groups xe2x80x94CO2CH3 and xe2x80x94OCH3 are on opposite sides of the olefinic bond of the propenoate group (the (E)-isomer). These (E)-isomers form a preferred embodiment of the invention.
The substituent R1 in compound (I) is optionally substituted aryl or optionally substituted heteroaryl. The term xe2x80x9carylxe2x80x9d includes phenyl in particular, and naphthyl. The term xe2x80x9cheteroarylxe2x80x9d includes 5- and 6-membered heterocyclic groups containing one or more of each of the heteroatoms O, S and N (preferably S or N), and fused benzenoid and heteroaromatic ring systems. Examples of heteroaryl groups which R1 may be are pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,2,3-, 1,2,4-, and 1,3,5-triazinyl, 1,2,4,5-tetrazinyl, thienyl, quinolinyl, isoquinolinyl, quinoxalinyl and benzothienyl.
Substituents which may be present in the optionally substituted aryl and heteroaryl moieties include one or more of the following; halogen, hydroxy, C1-4 alkyl (especially methyl and ethyl), C2-4 alkenyl (especially allyl), C2-4 alkynyl (especially propargyl), C1-4 alkoxy (especially methoxy), C2-4 alkenyloxy (especially allyloxy), C2-4 alkynyloxy (especially propargyloxy), halo(C1-4)alkyl (especially trifluoromethyl, trichloromethyl, and chloro- and bromomethyl), halo(C1-4)alkoxy (especially trifluoromethoxy), C1-4 alkylthio (especially methylthio), hydroxy(C1-4)alkyl (especially hydroxymethyl), (C1-4)alkoxy(C1-4)alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, optionally substituted aryl (especially optionally substituted phenyl), optionally substituted heteroaryl (especially optionally substituted pyridinyl or pyrimidinyl), optionally substituted aryloxy (especially optionally substituted phenoxy), optionally substituted heteroaryloxy (especially optionally substituted pyridinyloxy or pyrimidinyloxy), optionally substituted aryl(C1-4)alkyl (especially optionally substituted benzyl, optionally substituted phenethyl and optionally substituted phenyl n-propyl) in which the alkyl moiety is optionally substituted with hydroxy, optionally substituted heteroaryl(C1-4)alkyl (especially optionally substituted pyridinyl- or pyrimidinyl(C1-4)alkyl), optionally substituted aryl(C2-4)alkenyl (especially optionally substituted phenylethenyl), optionally substituted heteroaryl(C2-4)alkenyl (especially optionally substituted pyridinylethenyl or pyrimidinylethenyl), optionally substituted aryl(C1-4)alkoxy (especially optionally substituted benzyloxy), optionally substituted heteroaryl(C1-4)alkoxy (especially optionally substituted pyridinyl- or pyrimidinyl(C1-4)alkoxy), optionally substituted aryloxy (C1-4)alkyl (especially optionally substituted phenyloxymethyl), optionally substituted heteroaryloxy(C1-4)alkyl (especially optionally substituted pyridinyl- or pyrimidinyloxy(C1-4)-alkyl), acyloxy (especially acetyloxy and benzoyloxy), cyano, thiocyanato, nitro, xe2x80x94NRxe2x80x2Rxe2x80x3, xe2x80x94NHCORxe2x80x2, xe2x80x94NHCONRxe2x80x2Rxe2x80x3, xe2x80x94CONRxe2x80x2Rxe2x80x3, xe2x80x94COORxe2x80x2, xe2x80x94OSO2Rxe2x80x2, xe2x80x94SO2Rxe2x80x2, xe2x80x94CORxe2x80x2, xe2x80x94CRxe2x80x2xe2x95x90NRxe2x80x3 or xe2x80x94Nxe2x95x90CRxe2x80x2Rxe2x80x3 in which Rxe2x80x2 and Rxe2x80x3 are independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, optionally substituted aryl (especially optionally substituted phenyl) or optionally substituted aryl(C1-4)alkyl (especially optionally substituted benzyl). Substituents which may be present in the optionally substituted aryl and heteroaryl moieties include one or more of those aryl and heteroaryl substituents described immediately above.
Therefore, in yet another aspect, the invention provides compounds of the formula (I) as defined above in which R1 is aryl optionally substituted with one or more of hydroxy, C3-6 cycloalkyl(C1-4)alkyl, aryl(C1-4)alkoxy, aryloxy(C1-4)alkyl, acyloxy, CRxe2x80x2xe2x95x90NRxe2x80x3 or Nxe2x95x90CRxe2x80x2Rxe2x80x3 and Rxe2x80x2 and Rxe2x80x3 are independently hydrogen, C1-4 alkylthio, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C1-4 alkyl or C1-4 alkoxy.
In yet another aspect the invention provides compounds of the formula (I) as defined above in which R1 is aryl optionally substituted with one or more of NRxe2x80x2Rxe2x80x3, NHCORxe2x80x2, NHCONRxe2x80x2Rxe2x80x3, CONRxe2x80x2Rxe2x80x3, CO2Rxe2x80x2, OSO2Rxe2x80x2, SO2Rxe2x80x2 or CORxe2x80x2, Rxe2x80x2 is C3-6 cycloalkyl(C1-4)alkyl or benzyl and Rxe2x80x3 is hydrogen, C1-4 alkylthio, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C1-4 alkyl or C1-4 alkoxy.
In yet another aspect the invention provides the (E)-isomers of the compounds of the formula (Ia): 
in which Ab is selected from the group comprising 2-bromo; 3-iodo; 2-ethyl; 3-iso-propyl; 3-t-butyl; 3-trifluoro-methoxy; 3-amino; 4-phenyl; 2-carboxy; 3-methoxycarbonyl; 2-hydroxy; 2,3-difluoro; 3,5-difluoro; 2,3-dimethoxy; 2-fluoro-4-chloro; 2-chloro-5-fluoro; 2-fluoro-6-methyl; 3-methyl-4-fluoro; 3-fluoro-5-methoxy; 2-methoxy-3-fluoro; 2-chloro-4-methyl; 2-methyl-5-chloro; 2-chloro-6-methoxy; 3-methoxy-4-chloro; 3-methyl-5-methoxy; 2,4,5-trifluoro; 2,4,6-trichloro; 2,4,6-trimethyl; 2,6-difluoro-4-chloro; 2,6-dimethyl-4-fluoro, 2,3,5,6-tetrachloro; pentafluoro; and pentachloro.
Where substituents in the aryl or heteroaryl moieties are in adjacent positions they may join to form a fused ring, either aromatic or aliphatic, optionally containing one or more hetero atoms. Examples of R1 where substituents join to form fused rings are dibenzo-p-dioxinyl, thianthrenyl, phenoxathiinyl, dibenzofuranyl and dibenzothienyl.
When Y is oxygen and R1 is phenyl it is preferred that the phenyl ring is substituted. When Y is NR4 it is preferred that R1 is substituted to reduce the basicity of the NR4 nitrogen atom. This may be achieved by using as a substituent an electron withdrawing group.
When any of the substituents R2, R3, R4 and X are C1-4 alkyl, or C1-4alkoxy, the alkyl moiety can be in the form of straight or branched chains, that is, the moiety may be methyl, ethyl, n- or iso-propyl, or n-, sec-, iso- or t-butyl. Other references herein to C1-4 alkyl and C1-4 alkoxy carry the same meaning.
When any of the substituents R2, R3, R4 and X are C2-4 alkenyl, these groups can be in the form of straight or branched chains and, where appropriate, may have either the (E)- or the (Z)-configuration. Examples of such groups are vinyl, allyl, xe2x80x94C(CH3):CH2, and (E)- and (Z)-crotyl. Other references herein to C2-4 alkenyl carry the same meaning.
It is preferred that R2 and R3 are both hydrogen and that R4 is hydrogen or methyl.
When n is 2 or more, the substituents X may be the same or different. It is generally preferred, however, that n is 0 or 1.
In yet another aspect the invention provides compounds of the formula (Ib): 
especially the (E)-isomer, in which Y has the meaning given before; m is an integer of 1 to 5, and A is halo (especially fluoro or chloro), hydroxy, C1-4alkyl (especially methyl or ethyl), halo(C1-4)alkyl (especially halomethyl, particularly trifluoromethyl, difluoromethyl, fluoromethyl or trichloromethyl), C1-4 alkoxy (especially methoxy), halo(C1-4)alkoxy (especially trifluoromethoxy), phenyl, phenoxy, nitro, amino, acylamino (especially formamido and acetylamino), cyano, carboxy, C1-4 alkoxycarbonyl (especially methoxycarbonyl) or C1-4 alkylcarbonyloxy (especially acetoxy).
When m is 2 or more it is preferred that the substituents A, which may be the same or different, are fluoro, chloro, bromo, hydroxy, methyl, trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, methoxy, nitro, cyano, methoxycarbonyl or methylcarbonyloxy. Examples of combinations of the substituents Am when m is 2 or more are difluoro, dichloro, dimethyl, dimethoxy, fluoro-chloro, fluoro-methyl, fluoro-methoxy, chloro-methyl, chloro-methoxy, methyl-methoxy, trifluoro, trichloro, trimethyl, difluoro-chloro, dimethyl-fluoro, tetrachloro and pentafluoro.
In another aspect the invention provides compounds of the formula: 
especially the(E)-isomer, in which B is N or CH; Y has the meaning given before; p is 0 or an integer of 1 to 3 when B is N, or 0 or an integer of 1 to 4 when B is CH; and A1 has the meaning ascribed to A above.
Compounds are preferred in which the basicity of the nitrogen atom(s) of the heterocyclic ring is reduced. Accordingly it is preferred that Y is attached to a position ortho to a ring nitrogen atom, or a substituent A1 (especially methoxy) is attached to a position ortho to a ring nitrogen atom, or both.
When p is 2 or more, preferred values of A1 are those preferred values ascribed to A when m is 2 or more. Examples of combinations of the substituents A1p, when p is 2 or more are difluoro, dichloro, dibromo, chloro-fluoro, dichloro-fluoro, bromo-fluoro, bromo-chloro, fluoro-trifluoromethyl, chloro-trifluoromethyl, dichloro-trifluoromethyl, bromo-trifluoromethyl, fluoro-cyano, chloro-cyano, bromo-cyano, dicyano, cyano-trifluoro, chloro-hydroxy, bromo-hydroxy, chloro-methoxy, bromo-methoxy, chloro-nitro, cyano-nitro, methoxy-nitro, nitro-trifluoromethyl, chloro-acetyloxy, trifluoro, and when B is CH, cyano-trifluoro and tetrafluoro.
In another particular aspect, the invention provides the (E)-isomers of the compounds of the formula (Id): 
in which q is 0 or an integer of 1 to 5, D is halo, hydroxy, C1-4 alkyl, halo(C1-4)alkyl, C1-4 alkoxy, halo(C1-4)alkoxy or phenoxy; and E is hydrogen or halogen.
In another particular aspect, the invention provides the (E)-isomers of the compounds of the formula (Ie): 
in which B is N or CH; r is 0 or an integer of 1 to 3 when B is N or 0 or an integer of 1 to 4 when B is CH and D and E are as defined above.
In yet another particular aspect, the invention provides the (E)-isomers of the compounds of the formula (If): 
in which A is 3-bromo, 3-chloro or 4-chloro.
The invention is illustrated by the compounds listed in Table I which follows.
The invention is also illustrated by the compounds of the formula: 
in which R1, R2, R3 and X have the same combinations of meanings as each of the corresponding oxygen-linked compounds in Table I (i.e. when Y of Compound (I) is oxygen) and the meanings given to Compounds Nos. 1 to 3 in Table II below.
Compound No. 4 of Table II corresponds to Conpound No. 1 of Table I and Compound No. 5 corresponds to Compound No. 67 of Table I with respect to their meanings of R1, R2, R3 and X.
The invention is further illustrated by the compounds of the formula: 
in which R1, R2, R3 and X have the same combinations of meanings as each of the corresponding oxygen-linked compounds in Table I (i.e. where Y of Compound (I) is oxygen) and R4 is (a) hydrogen and (b) methyl.
In addition, R1, R2, R3, R4 and X may have the meanings given in Table III below.
The compounds of the invention of formula (I) may be prepared by the steps shown in Schemes I to V. Throughout these Schemes the terms R1, R2, R3, R4, X and Y are as defined above, R5 is hydrogen or a metal (such as sodium or potassium), R is an alkyl group, L is a leaving group such as halide (chloride, bromide or iodide), a CH3SO4-anion, or a sulphonyloxy-anion, and Z is a halogen (iodine, bromine or chlorine). Each of the transformations described in Schemes I to IV is performed at a suitable temperature and usually, though not always, in a suitable solvent.
The compounds of the invention of formula (I) can be prepared from the phenylacetates of formula (III) or the ketoesters of formula (VI) by the steps shown in Scheme I.
Thus compounds of formula (I) can be prepared by treatment of phenylacetates of formula (III) with a base (such as sodium hydride or sodium methoxide) and methyl formate. If a species of formula CH3L, wherein L is as defined above, is then added to the reaction mixture, compounds of formula (I) may be obtained. If a protic acid is added to the reaction mixture, compounds of formula (II) wherein R5 is hydrogen are obtained. Alternatively, the species of formula (II) wherein R5 is a metal (such as sodium) may themselves be isolated from the reaction mixture.
Compounds of formula (II) wherein R5 is a metal can be converted into compounds of formula (I) by treatment with a species of formula CH3L, wherein L is as defined above. Compounds of formula (II) wherein R5 is hydrogen can be converted into compounds of formula (I) by successive treatments with a base (such as potassium carbonate) and a species of general formula CH3L.
Alternatively, compounds of formula (I) can be prepared from acetals of formula (IV) by elimination of methanol under either acidic or basic conditions. Examples of reagents or reagent mixtures which can be used for this transformation are lithium di-isopropylamide; potassium hydrogen sulphate (see, for example, T Yamada, H Hagiwara and H Uda, J.Chem.Soc., Chemical Communications, 1980, 838, and references therein); and triethylamine, often in the presence of a Lewis acid such as titanium tetrachloride (see, for example, K Nsunda and L Heresi, J.Chem.Soc., Chemical Communications, 1985, 1000).
Acetals of formula (IV) can be prepared by treatment of methyl silyl ketene acetals of formula (V) wherein R is an alkyl group, with trimethyl orthoformate in the presence of a Lewis acid such as titanium tetrachloride (see, for example, K Saigo, M Osaki and T Mukaiyama, Chemistry Letters, 1976, 769).
Methyl silyl ketene acetals of formula (V) can be prepared from phenylacetates of formula (III) by treatment with a base and a trialkylsilyl halide of formula R3SiCl or R3SiBr, such as trimethylsilyl chloride, or a base (such as triethylamine) and a trialkylsilyl triflate of formula R3Sixe2x80x94OSO2CF3 (see, for example, C Ainsworth, F Chen and Y Kuo, J.Organometallic Chemistry, 1972, 46, 59).
It is not always necessary to isolate the intermediates (IV) and (V); under appropriate conditions, compounds of formula (I) may be prepared from phenylacetates of formula (III) in xe2x80x9cone potxe2x80x9d by the successive addition of suitable reagents listed above.
Alternatively, compounds of formula (I) can be prepared by treatment of ketoesters of formula (VI) with methoxymethylenation reagents such as methoxymethylenetriphenylphosphorane (see, for example, W Steglich, G Schramm, T Anke and F Oberwinkler, EP 0044448, 4.7.1980).
Ketoesters of formula (VI) may be prepared by methods described in the literature. Particularly useful methods include (i) the reaction of appropriate phenylmagnesium halides or phenyl-lithium species with dimethyl oxalate using the method described by L M Weinstock, R B Currie and A V Lovell, Synth.Commun., 1981, 11, 943 and references therein; (ii) oxidation of phenylacetates of formula (III) using selenium dioxide, generally in the absence of a solvent, and generally at a temperature above 100xc2x0 C.; and (iii) oxidation of mandelic acid esters using, for example, manganese oxide in a suitable solvent. 
Scheme II shows approaches by which phenylacetates of formula (III) may be prepared from 3-isochromanones of formula (IX).
Thus treatment of isochromanones of formula (IX) with species of formula R1YM, wherein R1 and Y are as defined above and M is a metal (such as sodium or potassium), gives phenylacetic acids of formula (VIII). The phenylacetic acids (VIII) may be converted into phenylacetates (III) by standard methods described in the literature.
Alternatively, isochromanones of formula (IX) may be converted into phenylacetates of formula (VII) wherein Z is a halogen atom (such as bromine) using HZ in methanol. This transformation may also be accomplished in 2 steps if the isochromanone (IX) is treated with HZ in a non-alcoholic solvent, and the resulting phenylacetic acid is then esterified using standard procedures (see, for example, I Matsumoto and J Yoshizawa, Jpn. Kokai (Tokkyo Koho) 79 138 536, 27.10.1979, Chem.Abs., 1980, 92, 180829h; and G M F Lim, Y G Perron and R D Droghini, Res.Discl., 1979, 188, 672, Chem.Abs., 1980, 92, 128526t). Phenylacetates of formula (VII) may be converted into phenylacetates of formula (III) by treatment with species R1YM, wherein R1, Y and M are as defined above.
Phenylacetates of formula (III) and the corresponding phenylacetic acids of formula (VIII) may also be prepared by numerous other methods described in the chemical literature. For example, several useful methods are described by D C Atkinson, K E Godfrey, B Meek, J F Saville and M R Stillings, J.Med.Chem., 1983, 26, 1353 and D C Atkinson, K E Godfrey, P L Meyers, N C Phillips, M R Stillings and A P Welbourn, J.Med.Chem., 1983, 26, 1361. Furthermore, many of the methods described for the preparation of 2-arylpropionic esters and acids by J-P Rieu, A Boucherle, H Cousse and G Mouzin, Tetrahedron, 1986, 42, 4095, are also applicable to the preparation of phenylacetates of formula (III) and phenylacetic acids of formula (VIII) using appropriate precursors wherein the substituents (R1Y)R2R3C- and X are already present. 
Isochromanones of formula (IX) may be prepared by methods described in the literature (see, for example, V B Milevskaya, R V Belinskaya, and L M Yagupol""skii, Zh.Org.Khim., 1973, 9, 2145; Chem.Abs., 80, 36954e).
Scheme III illustrates approaches to compounds of formula (I) from precursors containing a methyl beta-methoxypropenoate group. Thus propenoates of formula (X) are converted into compounds of formula (I) on treatment with species of formula R1YM, wherein R1, Y and M are as defined above. When R1 is an optionally substituted heteroaryl group containing at least one nitrogen atom (such as an optionally substituted pyridinyl group), species of formula R1YM may be ambident nucleophiles and as such may in principle react at either nitrogen or Y. For example, metal salts of 2-hydroxypyridine can react with alkylating agents at either nitrogen or oxygen to give the corresponding N-alkylpyridone or the 2-alkoxypyridine products, respectively. In this case, selective substitution on Y may be achieved using methods outlined in the literature (see, for example, G C Hopkins, J P Jonak, H J Minnemeyer and H Tieckelmann, J.Org.Chem., 1967, 32 4040. Compounds of formula (X) wherein L is a halogen such as bromine or chlorine may be prepared by halogenation of alkylbenzenes of formula (XII) using, for example, N-bromosuccinimide or sulphuryl chloride and methods described in the literature (see, for example, Modern Synthetic Reactions, Herbert House, 2nd Edition, Benjamin/Cummings, p.478 and references therein, and H.Matsumoto et al., Chemistry Letters, 1978, pp. 223-226). Compounds of formula (X) wherein L is a sulphonyloxy-group may be prepared from benzyl alcohols of formula (XI) using a sulphonyl halide and methods described in the literature. Treatment of benzyl alcohols with sulphonyl halides in the presence of a base sometimes leads, via a sulphonyloxy-derivative, to a benzyl halide, and this constitutes an alternative approach to compounds of formula (X) wherein L is a halogen.
Alternatively, when R1 is a sufficiently activated aryl or heteroaryl group, compounds of formula (I) may be prepared from compounds of formula (XIII) and species of formula R1L, wherein R1 and L are as defined above, often in the presence of a base such as sodium hydride, potassium tert-butoxide, or potassium carbonate.
The intermediates of formulae (XI), (XII) and (XIII) may be prepared from suitable phenylacetate or benzoylformate precursors using the transformations shown in Scheme I and described in the paragraphs above which refer to Scheme I. 
Some of the transformations shown in Scheme III can also be performed on intermediates containing, instead of the methyl beta-methoxypropenoate group, a group which can subsequently be converted into the methyl beta-methoxypropenoate group. For example, Scheme IV shows how the method used to transform (X) into (I) (Scheme III) can also be used to transform the halobenzene (xv) into the halobenzene (XIV) which can subsequently be converted into the compounds (I) using steps described in the paragraphs above or in the literature. 
When the term Y has the value NR4, additional approaches for the preparation of compounds of formula (I) are available, and these are shown in Scheme V. In Scheme V the term W is either the alpha-linked methyl beta-methoxypropenoate group CH3O.CH:C(CO2CH3)xe2x80x94, or it is a group or atom which may be converted into this group by the steps described in the paragraphs above, which is compatible with the conditions of the transformations of Scheme V.
Thus amides of formula (XVIII) may be reduced to amines of formula (XVI wherein R2xe2x95x90H) using reducing agents such as lithium aluminium hydride; and carbonyl compounds of formula (XVII) may be converted into amines of formula (XVI) by treatment with a primary or secondary amine of formula R1R4NH, wherein R1 and R4 are defined as above, in the presence of hydrogen and a hydrogenation catalyst or another reducing agent (see J March, xe2x80x98Advanced organic Chemistry : Reactions, Mechanisms and Structurexe2x80x99, 1968, McGraw-Hill Kogakusha Ltd, pages 668-670).
In further aspects the invention provides processes as hereindescribed for preparing the compounds of formula (I) and the intermediate chemicals of formulae (II) to (VI) and (VIII) used therein.
It also provides as intermediate chemicals the compounds of the formula (Ig): 
in which T is hydroxy, mercapto, formyl, hydroxymethyl, chloromethyl, bromomethyl, amino, carboxy or xe2x80x94CH2NHR in which R is alkyl or aryl (especially C1-4 alkyl or phenyl). These compounds include, in particular, the (E)-isomers.
It further provides as intermediate chemicals the compounds of the formula (Ih): 
in which Q is chloromethyl or formyl. These compounds include, in particular, the (E)-isomers.
The compounds of the invention are active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae on rice. Puccinia recondita, Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts e.g. coffee, pears, apples, peanuts, vegetables and ornamental plants. Erysiphe graminis (powdery mildew) on barley and wheat and other powdery mildews on various hosts such as Sphaerotheca macularis on hops, Sphaerotheca fuliginea on cucurbits (e.g. cucumber), Podosphaera leucotricha on apple and Uncinula necator on vines. Helminthosporium spp., Rhynchosporium spp., Septoria spp., Pseudocercosporella herpotrichoides and Gaeumannomyces graminis on cereals. Cercospora arachidicola and Cercosporidium personata on peanuts and other Cercospora species on other hosts for example sugar beet, bananas, soya beans and rice. Botrytis cinerea (grey mould) on tomatoes, strawberries, vegetables, vines and other hosts. Alternaria species on vegetables (e.g. cucumber), oil-seed rape, apples, tomatoes and other hosts. Venturia inaequalis (scab) on apples. Plasmopara viticola on vines. Other downy mildews such as Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions and other hosts and Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucurbits. Phytophthora infestans on potatoes and tomatoes and other Phytophthora spp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts. Thanatephorus cucumeris on rice and other Rhizoctonia species on various host such as wheat and barley, vegetables, cotton and turf.
Some of the compounds show a broad range of activities against fungi in vitro. They may also have activity against various post-harvest diseases of fruit (e.g. Penicillium digitatum and italicum and Trichoderma viride on oranges, Gloeosporium musarum on bananas and Botrytis cinerea on grapes).
Further some of the compounds may be active as seed dressings against Fusarium spp., Septoria spp., Tilletia spp., (bunt, a seed-borne disease of wheat), Ustilago spp. and Helminthosporium spp. on cereals, Rhizoctonia solani on cotton and Pyricularia oryzae on rice.
Some of the compounds can move acropetally and locally in the plant tissue. Moreover, the compounds may be volatile enough to be active in the vapour phase against fungi on the plant.
The invention therefore provides a method of combating fungi, which comprises applying to a plant, to a seed of a plant, or to the locus of the plant or seed, a fungicidally effective amount of a compound as hereinbefore defined, or a composition containing the same.
The compounds may also be useful as industrial (as opposed to agricultural) fungicides, e.g. in the prevention of fungal attack on wood, hides, leather and especially paint films.
Some compounds may exhibit plant growth regulating activity and may be deployed for this purpose at appropriate rates of application.
The compounds may be used directly as fungicides but are more conveniently formulated into compositions using a carrier or diluent. The invention thus provides fungicidal compositions comprising a compound as hereinbefore defined, and an acceptable carrier or diluent therefor.
The compounds can be applied in a number of ways. For example they can be applied, formulated or unformulated, directly to the foliage of a plant, to seeds or to other medium in which plants are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or paste formulation, or they can be applied as a vapour or as slow release granules. Application can be to any part of the plant including the foliage, stems, branches or roots, or to soil surrounding the roots, or to the seed before it is planted; or to the soil generally, to paddy water or to hydroponic culture systems. The invention compounds may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods.
The term xe2x80x9cplantxe2x80x9d as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic and eradicant treatment.
The compounds are preferably used for agricultural and horticultural purposes in the form of a composition. The type of composition used in any instance will depend upon the particular purpose envisaged.
The compositions may be in the form of dustable powders or granules comprising the active ingredient (invention compound) and a solid diluent or carrier, for example fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, Fuller""s earth, gypsum, diatomaceous earth and China clay. Such granules can be preformed granules suitable for application to the soil without further treatment. These granules can be made either by impregnating pellets of filler with the active ingredient or by pelleting a mixture of the active ingredient and powdered filler. Compositions for dressing seed may include an agent (for example a mineral oil) for assisting the adhesion of the composition to the seed; alternatively the active ingredient can be formulated for seed dressing purposes using an organic solvent (for example N-methylpyrrolidone, propylene glycol or dimethylformamide). The compositions may also be in the form of wettable powders or water dispersible granules comprising wetting or dispersing agents to facilitate the dispersion in liquids. The powders and granules may also contain fillers and suspending agents.
Emulsifiable concentrates or emulsions may be prepared by dissolving the active ingredient in an organic solvent optionally containing a wetting or emulsifying agent and then adding the mixture to water which may also contain a wetting or emulsifying agent. Suitable organic solvents are aromatic solvents such as alkylbenzenes and alkylnaphthalenes, ketones such as isophorone, cyclohexanone, and methylcyclohexanone, chlorinated hydrocarbons such as chlorobenzene and trichlorethane, and alcohols such as benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.
Suspension concentrates of largely insoluble solids may be prepared by ball or bead milling with a dispersing agent and including a suspending agent to stop the solid settling.
Compositions to be used as sprays may be in the form of aerosols wherein the formulation is held in a container under pressure in the presence of a propellant, eg. fluorotrichloromethane or dichlorodifluoromethane.
The invention compounds can be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating in enclosed spaces a smoke containing the compounds.
Alternatively, the compounds may be used in micro-encapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slow, controlled release of the active substance.
By including suitable additives, for example additives for improving the distribution, adhesive power and resistance to rain on treated surfaces, the different compositions can be better adapted for various utilities.
The invention compounds can be used as mixtures with fertilisers (eg. nitrogen-, potassium- or phosphorus-containing fertilisers). Compositions comprising only granules of fertiliser incorporating, for example coated with, the compound are preferred. Such granules suitably contain up to 25% by weight of the compound. The invention therefore also provides a fertiliser composition comprising a fertiliser and the compound of general formula (I) or a salt or metal complex thereof.
Wettable powders, emulsifiable concentrates and suspension concentrates will normally contain surfactants eg. a wetting agent, dispersing agent, emulsifying agent or suspending agent. These agents can be cationic, anionic or non-ionic agents.
Suitable cationic agents are quaternary ammonium compounds, for example cetyltrimethylammonium bromide. Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropyl-naphthalene sulphonates).
Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkyl phenols such as octyl- or nonyl-phenol and octylcresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, the condensation products of the said partial esters with ethylene oxide, and the lecithins. Suitable suspending agents are hydrophilic colloids (for example polyvinylpyrrolidone and sodium carboxymethylcellulose), and swelling clays such as bentonite or attapulgite.
Compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being diluted with water before use. These concentrates should preferably be able to withstand storage for prolonged periods and after such storage be capable of dilution with water in order to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. The concentrates may conveniently contain up to 95%, suitably 10-85%, for example 25-60%, by weight of the active ingredient. After dilution to form aqueous preparations, such preparations may contain varying amounts of the active ingredient depending upon the intended purpose, but an aqueous preparation containing 0.0005% or 0.01% to 10% by weight of active ingredient may be used.
The compositions of this invention may contain other compounds having biological activity, eg. compounds having similar or complementary fungicidal activity or which plant possess plant growth regulating, herbicidal or insecticidal activity.
A fungicidal compound which may be present in the composition of the invention may be one which is capable of combating ear diseases of cereals (eg. wheat) such as Septoria, Gibberella and Helminthosporium spp., seed and soil-borne diseases and downy and powdery mildews on grapes and powdery mildew and scab on apple etc. By including another fungicide, the composition can have a broader spectrum of activity than the compound of general formula (I) alone. Further the other fungicide can have a synergistic effect on the fungicidal activity of the compound of general formula (I). Examples of fungicidal compounds which may be included in the composition of the invention are carbendazim, benomyl, thiophanate-methyl, thiabendazole, fuberidazole, etridazole, dichlofluanid, cymoxanil, oxadixyl, ofurace, metalaxyl, furalaxyl, benalaxyl, fosetyl-aluminium, fenarimol, iprodione, prothiocarb, procymidone, vinclozolin, penconazole, myclobutanil, propamocarb, R0151297, diniconazole, pyrazophos, ethirimol, ditalimfos, tridemorph, triforine, nuarimol, triazbutyl, guazatine, triacetate salt of 1,1xe2x80x2-iminodi(octamethylene)diguanidine, buthiobate, propiconazole, prochloraz, flutriafol, hexaconazole, (2 RS, 3 RS)-2-(4-chlorophenyl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol, fluzilazole, triadimefon, triadimenol, diclobutrazol, fenpropimorph, pyrifenox, fenpropidin, chlorozolinate, imazalil, fenfuram, carboxin, oxycarboxin, methfuroxam, dodemorph, BAS 454, blasticidin S. kasugamycin, edifenphos, Kitazin P, cycloheximide, phthalide, probenazole, iso-prothiolane, tricyclazole, 4-chloro-N-(cyano(ethoxy)-methyl)benzamide, pyroquilon, chlorbenzthiazone, neoasozin, polyoxin D, validamycin A, mepronil, flutolanil, pencycuron, diclomezine, phenazin oxide, nickel dimethyldithiocarbamate, techlofthalam, bitertanol, bupirimate, etaconazole, hydroxyisoxazole, streptomycin, cyprofuram, biloxazol, quinomethionate, dimethirimol, 1-(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea, fenapanil, tolclofos-methyl, pyroxyfur, polyram, maneb, mancozeb, captafol, chlorothalonil, anilazine, thiram, captan, folpet, zineb, propineb, sulphur, dinocap, dichlone, chloroneb, binapacryl, nitrothal-isopropyl, dodine, dithianon, fentin hydroxide, fentin acetate, tecnazene, quintozene, dicloran, copper containing compounds such as copper oxychloride, copper sulphate and Bordeaux mixture, and organomercury compounds. The compounds of general formula (I) can be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.
Suitable insecticides which may be incorporated in the composition of the invention include pirimicarb, dimethoate, demeton-s-methyl, formothion, carbaryl, isoprocarb, XMC, BPMC, carbofuran, carbosulfan, diazinon, fenthion, fenitrothion, phenthoate, chlorpyrifos, isoxathion, propaphos, monocrotophas, buprofezin, ethroproxyfen and cycloprothrin.
Plant growth regulating compounds are compounds which control weeds or seedhead formation, or selectively control the growth of less desirable plants (eg. grasses).
Examples of suitable plant growth regulating compounds for use with the invention compounds are the gibberellins (eg. GA3, GA4 or GA7), the auxins (eg. indoleacetic acid, indolebutyric acid, naphthoxyacetic acid or naphthylacetic acid), the cytokinins (eg. kinetin, diphenylurea, benzimidazole, benzyladenine or benzylaminopurine), phenoxyacetic acids (eg. 2,4-D or MCPA), substituted benzoic acid (eg. triiodobenzoic acid), morphactins (eg. chlorfluoroecol), maleic hydrazide, glyphosate, glyphosine, long chain fatty alcohols and acids, dikegulac, paclobutrazol, fluoridamid, mefluidide, substituted quaternary ammonium and phosphonium compounds (eg. chloromequat chlorphonium or mepiquatchloride), ethephon, carbetamide, methyl-3,6-dichloroanisate, daminozide, asulam, abscisic acid, isopyrimol, 1-(4-chlorophenyl)-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid, hydroxybenzonitriles (eg. bromoxynil), difenzoquat, benzoylprop-ethyl 3,6-dichloropicolinic acid, fenpentezol, inabenfide, triapenthenol and tecnazene.
The following Examples illustrate the invention. Throughout the Examples, the term xe2x80x98etherxe2x80x99 refers to diethyl ether, magnesium sulphate was used to dry solutions, and solutions were concentrated under reduced pressure. Reactions involving water-sensitive intermediates were performed under an atmosphere of nitrogen and solvents were dried before use, where appropriate. Unless otherwise stated, chromatography was performed on a column of silica gel as the stationary phase. Where shown, infrared and NMR data are selective; no attempt is made to list every absorption in all cases. 1H NMR spectra were recorded using CDCl3-solutions unless otherwise stated. The following abbreviations are used throughout: